Dissertation

Increased Secretion of Il-6 in Bipolar Patient iPsc-Derived Astrocytes Decreases Neuronal Synaptic Activity

Racha, Vipula

2020

Overview

Bipolar disorder (BD) is a neuropsychiatric disease characterized by intermittent episodes of mania and depression that detrimentally affects a person’s ability to carry out day-to-day tasks. Life expectancy is reduced by 10 to 15 years along with an increased suicide rate and comorbidities such as cardiovascular disease and diabetes. Studies have shown that synaptic plasticity and inflammation play a major role in the pathophysiology of bipolar disorder, but how they contribute is still unknown. Astrocytes, an important glial cell type in the brain, are significant in both synaptic plasticity and inflammation but are currently understudied in bipolar disorder. Therefore, we wanted to know the effect that astrocytes derived from induced pluripotent stem cells (iPSCs) from bipolar patients have on the synaptic activity of control neurons measured via multiple electrode array during inflammatory conditions. BD astrocytes showed increased secretion of IL-6, an inflammatory cytokine, when activated with IL-1b, a pro-inflammatory cytokine. Both co-culture with BD astrocytes and addition of conditioned media from BD astrocytes decreased action potentials in control neurons, which was rescued by adding an IL-6 blocking antibody. Our results suggest that increased IL-6 secretion in response to inflammatory stimuli in BD astrocytes may lead to altered neuronal activity in BD patients that could contribute to the bipolar phenotype. These results may further elucidate the etiology of BD and help scientists understand the role of astrocytes and inflammatory proteins in BD.

• Publisher: ProQuest Dissertations & Theses
• Subject: Endocrinology / Mental health / Neurosciences / Pathology / Psychobiology
• ISBN: 9798678124487